Mini Review Curr Trends Biomedical Eng & Biosci Volume 16 Issue 4 - October 2018 Copyright © All rights are reserved by Ravi Kant Upadhyay DOI: 10.19080/CTBEB.2018.16.555945 Use of Animal Venom Peptides/Toxins in Cancer Therapeutics Ravi Kant Upadhyay* Department of Zoology, D D U Gorakhpur University, India Submission: March 27, 2018; Published: October 01, 2018 *Corresponding author: Ravi Kant Upadhyay, Department of Zoology, D D U Gorakhpur University, India, Email: Abstract Animal venoms possess variety of toxins/proteins/peptides which act as ionic channel inhibitors and target vital physiological processes. Toxin peptides isolated from honey bee, wasp and scorpion show membrane binding, growth inhibition and strong cytolytic properties. These also inhibit angiogenesis and induce caspase-dependent apoptosis in melanoma cells through the intrinsic mitochondrial pathway protecting the experimental animals against tumor development. These toxin peptides exert cytotoxic effects on human oral cancer cells by inducting apoptosis via a p53-dependent intrinsic apoptotic pathway. These can be used as cancer therapeutic agents by loading them in liposomes. This does enhancement in the number of apoptotic cells. In addition, toxins enhance G0/G1 enrichment upon treatment of cancer cells. Further, encapsulatedlead to increase honey in their bee, wasptarget and specificity scorpion against venoms cancer exert muchcells, shortenpotent anti-cancer cell survival, effect and on produce many cancer higher cells reactive lines. oxygen species (ROS), and effects because of charge optimization. After their improvement they show superiority over the conventional chemical drugs as an increase in net Upon slight chemical modifications animal toxins could gear up higher selectivity, show much improved target specificity and lesser toxic incharge GBM of immunotherapy. the peptide, its hydrophobicityVenom toxins/peptides and anionicity are good and natural fluidity sources of the target of compounds/molecules cell membranes. It primarily which could imparts act effect as prototype through orbiophysical template whichinteraction can be with used the for target development cell membrane. of new Toxin therapeutic peptides agents are best and candidate best tools as for they diagnosis selectively of not target only malignant for cancer gliomas but also and for playother significant diseases. role Keywords: Animal toxins peptides; Channel blockers; Anti-cancer effects; Drug delivery; Therapeutic applications Introduction Figure 1: Showing various steps of cancer progression and its strong inhibition sites. Cancer is a complex disease that shows abnormal cell growth are evoked due to environmental stress, microbial infection, food with invasion of surrounding cells and tissues. Cancer is caused by adulteration, smoke, tobacco, ionizing radiation, heavy metal a progressive accumulation of multiple genetic mutations which exposure, and multiple genetic reasons. Approximately 5–10% Curr Trends Biomedical Eng & Biosci 16(4): CTBEB.MS.ID.555945 (2018) 00106 Current Trends in Biomedical Engineering & Biosciences of cancers are due to inherited genetic defects inherited from The process of malignant transformation of cells could be used parents. Cancer is preventive if proper care and therapeutic dietary by using animal toxin peptides because they show cytotoxicity to cancer cells and work in a concert at several target sites and show from a single neoplastic cell possessing a regulatory defect, which measures are maintained (Figure 1). Most cancer cells are derived is inherited by the clonal progeny. Unregulated growth in vivo: wider Animal therapeutic venom applications is unique (Figurenatural 1).products synthesized by Cancer cells do not respond to normal regulatory mechanisms, venoming animals. It is complex mixture of various toxins/ they can proliferate indefinitely and show unregulated growth. venom in self defense or to immobilize the prey for predation some cancer cells to grow beyond the boundaries of their tissue proteins, peptides, certain elements and acids. Animals inflict Cancerous activity alters tissue-specific affinity that enables and digestion. Venom toxins cause multiple symptoms in stung of origin. These cells can metastasize and grow in diverse tissue animals and impart inhibitory effects on electrophysiology of ion channels. They act very fast and also cause respiratory paralysis “wrong” tissues; this property may account for the tendency of sites. Other cancer cells appear to acquire affinity for specific but or cardiac arrest in prey. There are wide varieties of natural certain cancers to metastasize preferentially to particular tissue toxins, i.e. neurotoxins, myotoxins, cardiotoxins, hematoxins and sites. catalytic enzymes which act by diverse mechanisms on different cell types and cause multiple dysfunctions on the target cell cells, eventually leading to death of the prey [1]. There are specific categories of oncogenes that inhibit tumors showed altered MHC expression and the wrong biological cellular proliferation and regulate programmed cell death. Some The variety of proteins and peptides have been isolated from consequence regarding cell growth and cell proliferation. There honey bee venom and wasp venom which include melittin, are three important attacking points to control cancer invasion adiapin, apamine, bradykinin, cardiopep, mast cell degranulating of tissues i.e. by activating tumor suppressor oncogenes, stop peptide, mastoparan, phospholipase A2 and secapin. There are adhesion of cancer cells, growth and proliferation. Treatment of several venom proteins and peptides with possible therapeutic normal cultured cells with chemical carcinogens, irradiation, and certain viruses can alter the morphology and growth properties of act very fast and target ion channels use as diagnostics and the cells. In some case this process, referred to as transformation, applications from bees and wasps and szcorpions. Some of these are therapeutically important [2]. Certain naturally occurring makes the cells able to induce tumors when they are injected toxins from scorpion venom are used as molecular probes for into animals; such cells are said to have undergone malignant + transformation, and they often exhibit in vitro culture properties Many of these toxins are selective for particular K+ channel similar to those of cancer. They have decreased requirements for investigating the potassium (K ) and calcium binding channels. subtypes and gear a quick physiological effect on mammalian growth factors and serum, are no longer anchorage, dependent, grow in a density-independent fashion—and they are immortal. brain by attacking on cell membranes (Figure 2). MMTX No inhibition No inhibition Scorpion toxins Mammalian brain Figure 2: Showing action of scorpion neurotoxins on neuron membrane and its effect on mammalian brain. Wasp venom is also a rich source of therapeutically important cationic tetradecapeptide which is isolated from the venom of the toxins which includes short cationic peptides, kinins and wasp Vespula lewisii. It exhibits a wide variety of biological effect mainly tumor cell cytotoxicity and induce histamine release from mast cells. Mastoparan causes melanoma cell death by induction polyamines (Table 1). These are used in the treatment of pain, of caspase-dependent mitochondrial apoptosis pathway in murine inflammatory disease, and neurodegenerative diseases such as epilepsy and aversion. Mastoparan is α-helical and amphipathic How to cite this article: Ravi K U. Use of Animal Venom Peptides/Toxins in Cancer Therapeutics. Curr Trends Biomedical Eng & Biosci. 2018; 16(4): 00107 555945. DOI: 10.19080/CTBEB.2018.16.555945. Current Trends in Biomedical Engineering & Biosciences model of B16F10-Nex2 cells. It shows cytolytic activity in tumor cathepsin B and become active. tumor proteases, such as the metalloproteinase-2 (MMP-2) or cells. Upon conjugation to poly (l-glutamic acid) PGA polymer throughTable 1: Showingspecific Toxincleavage Peptides sequences Isolated it from binds Different to over-expressed Animals, with their Physiological Effects and Therapeutic use. Animal Name of Toxin Peptide Physiological Effect Toxin Category Therapeutic use wasp venom Anti-rheumatic dilates blood Kinins and polyamines Cytotoxic Protonectarina vessels via the release of Vespa, Parapolybia, Inflammation , Polistes Membrane-active amphipathic Cytotoxic, hemolytic Anticancer effects and induce andWasp Protopolybia. venom Mastoparan peptide, it causes the secretion insert into the membrane caspase-dependent apoptosis of histamine from mast cells bilayer in melanoma cells, Melittin Neuro and cytotoxic, Melittin displays anti-prolif- Wasp and honey bee damages skeletal muscles nerve terminals and muscle erative activity to cancer cells venom and inhibits cell regen- Severely actscells upon motor in vivo eration - tions, bradykinin elevate vas- Antimicrobial and anticancer Wasp venom Bradykinin cularImpose permeability inflammatory and reaccause via G protein – coupled agents vasodilatation in some arteries Show biologicalreceptors. effects and vein Activities against other Honey bee venom and Antimicrobial and anti- gram-negative bacteria Adiapin, apamine wasp venom cancer agents and Gram-positive Polycationic peptides Wasp and honey bee Antimicrobial and anti- Hyperalgesic and Cardiopep venom cancer agents edematogenic Wasp and honey bee Mast cell degranulating Polycationic peptides Antimicrobial and anticancer Activation of G protein venom